Expression and amplification of eIF-5A2 in human epithelial ovarian tumors and overexpression of EIF-5A2 is a new independent predictor of outcome in patients with ovarian carcinoma
Introduction
Ovarian cancer is a major cause of death among all gynecological malignancies. It is the seventh most common cancer in women worldwide and is the fourth leading cause of death from cancer among American women [1]. Recently, its incidence has been increasing in Asian countries such as China and Singapore [2]. Because of its insidious onset, 70% of ovarian cancer patients were diagnosed at advanced stage, and the prognosis is very poor with a 5-year survival rate of < 20% [3]. Ovarian carcinoma is the most common histopathological type of ovarian cancer. The development of ovarian carcinoma is considered as a multi-step process involving multiple genetic changes [4]. Recurrent chromosomal changes in ovarian carcinoma have been extensively analyzed by comparative genomic hybridization (CGH) with several amplified regions including 3q or parts of 3q, being reported [5], [6], [7], [8]. Amplification of 3q also has been detected frequently in other solid malignant tumors including esophageal carcinoma [9], lung carcinoma [10], gastric carcinoma [11], colorectal carcinoma [12] and other neoplasms [13], [14], suggesting that human chromosome 3q contains oncogenes related to tumorigenesis and progression of a number of different solid tumors.
Using a chromosome microdissection-hybrid selection method, we have previously isolated a novel candidate oncogene, eIF-5A2 (eukaryotic initiation factor 5A2), from a primary ovarian cancer cell line UACC-1598 containing a high-copy-number amplification of 3q26 [15]. Recently, tumorigenic characteristics of eIF-5A2 have been demonstrated by both in vitro and in vivo assays [16]. Up-regulated expression of eIF-5A2 was observed in gastric and colorectal carcinomas and it was associated with a higher risk of tumor metastasis [17], [18], [19]. These findings suggest that eIF-5A2 might function as a putative oncogene in the tumorigenesis of several types of human cancers. In this study, the expression dynamics of EIF-5A2 in a series of human ovarian tissue, normal and pathological, non-neoplastic and neoplastic, were examined. The clinicopathological and prognostic significance of overexpression of EIF-5A2 in our ovarian carcinoma cohorts was also assessed.
Section snippets
Patients and tissue specimens
A total of 170 epithelial ovarian tumors (benign, borderline and carcinomatous) and 30 normal ovaries were obtained from archives of paraffin-embedded tissues between 1990 and 2001 at the Department of Pathology, Cancer Center and the First affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. The cancer cases selected were based on availability of resection tissue and follow-up data. The ovarian tumor cases encompassed 110 histologically confirmed invasive carcinomas, 30 borderline
EIF-5A2 expression in ovarian tissues
For EIF-5A2 IHC staining in ovarian tissues, because the expression of EIF-5A2 in the surface epithelium of all 30 normal ovarian surface epithelium was negative (0) or weak (1) (Fig. 1A), the staining index in the normal ovaries was determined to be less or equal to 3. Therefore, we designated the staining index of 0–3 as the normal expression of EIF-5A2 (Figs. 1A and B), while staining index of 4–12 was depicted as overexpression of this protein (Figs. 1C and E). Using this designation, the
Discussion
Recently, we have isolated a novel candidate oncogene, eIF-5A2, from a primary ovarian cancer cell line UACC-1598 containing a high-copy-number amplification of 3q26 [15]. To investigate whether or not up-regulated expression of EIF-5A2 is involved in the pathogenesis of ovarian carcinoma, in the present report, the expression of EIF-5A2 was examined firstly by IHC in normal ovaries, benign and borderline epithelial ovarian tumors, and malignant epithelial cancers. Our results demonstrate that
Conflict of interest statement
The authors declare that there are no conflicts of interest.
Acknowledgments
This study was supported in part by the Major State Basic Research Program of China (2006CB910104), the Nature Science Foundation of China (No.30772334 and 30772475), Key Special Project of Guangdong Science and technology Agency (2005A30801001) and Hong Kong Research Grant Council Grant (HKU7656/07M).
References (29)
- et al.
Recurrent chromosome alterations in primary ovarian carcinoma of Chinese women
Cancer Genet. Cytogenet.
(2002) - et al.
A broad amplification pattern at 3q in squamous cell lung cancer—a fluorescence in situ hybridization study
Cancer Genet. Cytogenet.
(2000) - et al.
Recurrent chromosome changes in 62 primary gastric carcinomas detected by comparative genomic hybridization
Cancer Genet. Cytogenet.
(2000) - et al.
Recurrent genetic alterations in 26 colorectal carcinomas and 21 adenomas from Chinese patients
Cancer Genet. Cytogenet.
(2003) - et al.
Overexpression of EIF-5A2 is associated with metastasis of human colorectal carcinoma
Hum. Pathol.
(2008) - et al.
Human eIF5A2 on chromosome 3q25-q27 is a phylogenetically conserved vertebrate variant of eukaryotic translation initiation factor 5A with tissue-specific expression
Genomics
(2001) - et al.
Effect of initiation factor eIF-5A depletion on protein synthesis and proliferation of Saccharomyces cerevisiae
J. Biol. Chem.
(1994) - et al.
Marked elevation of hypusine formation activity on eukaryotic initiation factor 5A in v-HA-RAS transformed mouse NIH3T3 cells
Cancer Lett.
(1997) - et al.
Recent progress in understanding mechanisms of mammalian DNA amplification
Cell
(1989) - et al.
Cancer incidence and mortality, 1973–1995, a report card for the U.S.
Cancer
(1998)